Epidemiological studies indicate that ultra violet (UV) radiation causes skin damage and is a major environmental agent in skin cancer development. The effects of COX-1 and COX-2 deficiency, as well as COX-1 and COX-2 selective inhibitors, in acute UV dose induced skin damage have been studied. The results indicate that mice deficient in COX-2, but not COX-1, exhibit dose dependent increases in epidermal skin damage and cell death compared to wild type mice. Levels of apoptosis were increased about 2.5 -fold in COX-2 null mice compared to COX-1 null or wild type mice. The prostaglandin E2 receptors, EP2 and EP4, have been demonstrated to be involved in COX-2's protective effect against UV induced skin damage. Furthermore, the signaling pathways activated by EP2 and EP4 in the protection of UVB induced skin damage have been partially elucidated, and shown to involve PKA and Akt, respectively.